Abstract: Spurred by recent advances in materials chemistry, molecular pharmaceutics, and nanobiotechnology, stimuli-responsive ​“smart” systems offer opportunities for precisely delivering drugs in dose-, spatial- and temporal-controlled manners. In this talk, I will discuss our ongoing efforts in developing physiological signal-triggered bio-responsive drug delivery systems, especially those based on artificial cells or engineered cells. I will first present the glucose-responsive synthetic systems for biomimetic delivery of insulin for diabetes treatment. Bio-responsive microneedle patches and vesicle fusion-mediated synthetic beta cells will be emphasized. I will further discuss the local and targeted delivery of immunomodulatory therapeutics for enhanced cancer therapy. Our latest study utilizing platelets and injectable hydrogels for targeted/local delivery of immune checkpoint inhibitors will be specifically introduced.